🧬 Alkaptonuria is a rare autosomal recessive metabolic disorder. It leads to accumulation of homogentisic acid → dark pigmentation of connective tissues (ochronosis) + early arthritis. Classically: urine that darkens on standing! ⚗️

ℹ️ About

Autosomal recessive inherited cause of arthritis.
Dark pigmentation of cartilage and connective tissues = Ochronosis.

⚙️ Aetiology

Deficiency of homogentisic acid oxidase.
Enzyme encoded on chromosome 3q.
Accumulated homogentisic acid binds collagen → tissue fragility and degeneration.

👩‍⚕️ Clinical Features

👁️ Blue-black pigmentation of sclerae and ear cartilage (first sign).
🦴 Crystal deposition in joints → destructive arthritis, especially spine, hips, knees.
🎧 Ochronosis: darkening of pinna and cartilage.
🧴 Sweat and connective tissues may be pigmented.
⚗️ Urine clear on voiding, but turns dark on standing or with alkali.
Early-onset osteoarthritis due to brittle, pigmented cartilage.

🔬 Investigations

Urine darkens on exposure to air or alkali (bedside clue!).
Confirm with ↑ urinary homogentisic acid (GC-MS or HPLC).
Genetic testing for HGD gene mutation if needed.

💊 Management

Low protein diet (↓ phenylalanine & tyrosine intake).
Vitamin C (ascorbic acid) → may ↑ renal clearance of homogentisic acid.
Symptomatic management of arthritis (analgesia, physio, joint replacement if severe).
Experimental: Nitisinone (tyrosine metabolism inhibitor) reduces homogentisic acid production.

Ochronosis in alkaptonuria

Cases - Alkaptonuria

Case 1 - Dark urine in childhood 🍼: A 6-year-old boy is brought by parents because his nappies consistently turn dark brown after a few hours. He is otherwise well. Urine test: homogentisic acid positive. Diagnosis: alkaptonuria, a rare autosomal recessive disorder of tyrosine metabolism due to deficiency of homogentisate oxidase. Parents are counselled on long-term monitoring.
Case 2 - Ochronosis and joint disease 🤕: A 52-year-old man presents with progressive back stiffness, knee pain, and bluish-black discolouration of ear cartilage and sclerae. Past history reveals dark urine since youth but never investigated. X-rays: calcification of intervertebral discs and degenerative changes in large joints. Diagnosis: adult presentation of alkaptonuria with ochronosis. Managed with analgesia, joint replacement consideration, and metabolic specialist referral.

Teaching Point 🩺: Alkaptonuria is a rare metabolic disorder (1 in 250,000) that causes accumulation of homogentisic acid. Classic clues are dark urine in childhood and later ochronosis with early osteoarthritis. Treatment is supportive; nitisinone is under study.

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Alkaptonuria